Genetic variants associated with fasting glucose and insulin concentrations in an ethnically diverse population: results from the Population Architecture using Genomics and Epidemiology (PAGE) study

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  • Fesinmeyer, Megan D
    • Other Affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle WA, USA
  • Meigs, James B
    • Other Affiliation: General Medicine Division, Department of Medicine, Harvard Medical School, Boston MA, USA
  • North, Kari
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology, School of Medicine, Carolina Center for Genome Sciences
  • Schumacher, Fredrick R
    • Other Affiliation: Department of Preventive Medicine, Keck School of Medicine / Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA
  • Bůžková, Petra
    • Other Affiliation: Department of Biostatistics, University of Washington, Seattle, WA, USA
  • Franceschini, Nora
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Haessler, Jeffrey
    • Other Affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle WA, USA
  • Goodloe, Robert
    • Other Affiliation: Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, TN, USA
  • Spencer, Kylee L
    • Other Affiliation: Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, TN, USA
  • Voruganti, Venkata
    • Other Affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA
  • Howard, Barbara V
    • Other Affiliation: MedStar Research Institute, Georgetown University, Hyattsville, MD, USA
  • Jackson, Rebecca
    • Other Affiliation: Department of Internal Medicine, Ohio State Medical Center, Columbus, OH, USA
  • Kolonel, Laurence N
    • Other Affiliation: Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA
  • Liu, Simin
    • Other Affiliation: Department of Epidemiology, University of California, Los Angeles, CA, USA
  • Manson, JoAnn E
    • Other Affiliation: Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
  • Monroe, Kristine R
    • Other Affiliation: Department of Preventive Medicine, Keck School of Medicine / Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA
  • Mukamal, Kenneth
    • Other Affiliation: Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
  • Dilks, Holli H
    • Other Affiliation: Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, TN, USA
  • Pendergrass, Sarah A
    • Other Affiliation: Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, PA, USA
  • Nato, Andrew
    • Other Affiliation: Department of Genetics, Rutgers University, Piscataway, NJ, USA
  • Wan, Peggy
    • Other Affiliation: Department of Preventive Medicine, Keck School of Medicine / Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA
  • Wilkens, Lynne R
    • Other Affiliation: Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA
  • Marchand, Loic
    • Other Affiliation: Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA
  • Ambite, José
    • Other Affiliation: Information Sciences Institute, University of Southern California, Marina del Rey, CA, USA
  • Buyske, Steven
    • Other Affiliation: Department of Genetics, Rutgers University, Piscataway, NJ, USA; Department of Statistics & Biostatistics, Rutgers University, Piscataway, NJ, USA
  • Florez, Jose C
    • Other Affiliation: General Medicine Division, Department of Medicine, Harvard Medical School, Boston MA, USA
  • Crawford, Dana C
    • Other Affiliation: Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, TN, USA
  • Hindorff, Lucia A
    • Other Affiliation: Office of Population Genomics, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA
  • Haiman, Christopher A
    • Other Affiliation: Department of Preventive Medicine, Keck School of Medicine / Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA
  • Peters, Ulrike
    • Other Affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle WA, USA
  • Pankow, James S
    • Other Affiliation: Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis MN, USA
Abstract
  • Abstract Background Multiple genome-wide association studies (GWAS) within European populations have implicated common genetic variants associated with insulin and glucose concentrations. In contrast, few studies have been conducted within minority groups, which carry the highest burden of impaired glucose homeostasis and type 2 diabetes in the U.S. Methods As part of the 'Population Architecture using Genomics and Epidemiology (PAGE) Consortium, we investigated the association of up to 10 GWAS-identified single nucleotide polymorphisms (SNPs) in 8 genetic regions with glucose or insulin concentrations in up to 36,579 non-diabetic subjects including 23,323 European Americans (EA) and 7,526 African Americans (AA), 3,140 Hispanics, 1,779 American Indians (AI), and 811 Asians. We estimated the association between each SNP and fasting glucose or log-transformed fasting insulin, followed by meta-analysis to combine results across PAGE sites. Results Overall, our results show that 9/9 GWAS SNPs are associated with glucose in EA (p = 0.04 to 9 × 10-15), versus 3/9 in AA (p= 0.03 to 6 × 10-5), 3/4 SNPs in Hispanics, 2/4 SNPs in AI, and 1/2 SNPs in Asians. For insulin we observed a significant association with rs780094/GCKR in EA, Hispanics and AI only. Conclusions Generalization of results across multiple racial/ethnic groups helps confirm the relevance of some of these loci for glucose and insulin metabolism. Lack of association in non-EA groups may be due to insufficient power, or to unique patterns of linkage disequilibrium.
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Resource type
  • Article
Rights statement
  • In Copyright
Rights holder
  • Megan D Fesinmeyer et al.; licensee BioMed Central Ltd.
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Journal title
  • BMC Medical Genetics
Journal volume
  • 14
Journal issue
  • 1
Page start
  • 98
Language
  • English
Is the article or chapter peer-reviewed?
  • Yes
ISSN
  • 1471-2350
Bibliographic citation
  • BMC Medical Genetics. 2013 Sep 25;14(1):98
Publisher
  • BioMed Central Ltd
Access right
  • Open Access
Date uploaded
  • July 16, 2016

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